Age-related macular degeneration is the most common cause of severe visual impairment in individuals over the age of fifty-five (Adler, Curcio, Hicks, Price, &Wong, 1999;Friedman et al., 2004). Geographic atrophy is an advanced stage of age-related macular degeneration that currently has no treatment. As the US population ages over the next decade, the number of individuals with geographic atrophy is expected to increase by fifty percent (Friedman et al., 2004). The cause of the disease is not understood, which is impeding the development of treatments for it. Several cell types in the retina have been implicated in geographic atrophy, but it is impossible to examine the microscopic changes that these cells undergo in the living human eye using current clinical tools. High resolution retinal imaging methods, which use adaptive optics, a method for measuring and correcting the optical aberrations present in all eyes, allow for microscopic examination of individual cells in the living human retina. The objective of this project is to apply high resolution retinal imaging with adaptive optics to geographic atrophy patients to simultaneously image three independent cell mosaics in the retina: cones, rods and retinal pigment epithelium, and to track them as the disease progresses. High resolution retinal imaging of the light sensitive rod and cone photoreceptors and of the retinal pigment epithelium (another retinal cell type that is critical to vision) will allow us to see microscopic changes due to geographic atrophy that have never before been seen in the living human eye. This project will provide insight into how geographic atrophy progresses through these cell types, including the sequence of cell loss, which will allow us to discriminate between different competing theories regarding the origin of geographic atrophy. This understanding will be critical for targeting therapeutic interventions for geographic atrophy to the appropriate cell type. Not only may the application of adaptive optics imaging methods allow us to discriminate between different theories of geographic atrophy, it may also provide a way to detect the disease earlier in its time-course and eventually may provide a valuable outcome measure for the development of therapies for geographic atrophy. [Using high resolution retinal densitometry in AOSLO, we will assess changes in photoreceptor function that accompany structural changes in geographic atrophy.] PUBLIC HEALTH RELEVANCE: Geographic atrophy is an advanced stage of age-related macular degeneration, a disease that is the most common cause of severe visual impairment in individuals over the age of fifty-five. This project aims to develop a comprehensive understanding of the origin of geographic atrophy and its progression by using advanced imaging methods to see how different cells in the eye are changed as a result of disease. This understanding is critical for the development of treatments for geographic atrophy, a disease that is expected to affect more Americans as the population ages.